Monday, December 31, 2012

GMOs Part 2: How The Digestive System Works

In my last post, I gave an overview of why there's no scientific basis for claiming that GMOs by definition are harmful for human health, focusing mostly on the molecular biology angle. Now, I'd like to add on to that by describing how food gets digested on a molecular level. If GMOs are going to be harmful, it's going to happen on this scale, and it's going to be unique to the specific GMO in question. Hopefully, both pieces together will help you spot what the real issues are and what is BS in the GMO debate. Not coincidentally, a major concept here is that DNA is DNA, just like in the molecular biology discussion.

Everything we ingest is essentially made up of four basic types of macromolecules: sugars, fats (or lipids), proteins, and nucleic acids. We're only concerned with the latter two, because all life, genetically modified or not uses the same range of sugars and fats. Let's start with how proteins are digested. Remember, the point of a GMO is to get an organism to code for a specific different, or set of different proteins that it wouldn't otherwise produce. Proteins are fascinating molecules, and I would totally have enjoyed an entire course on just them alone. Depending on its sequence of amino acids, a protein can be an enzyme, a hormone, or used for structural purposes, like collagen or the exoskeleton of a crustacean. Our digestive system is full of hundreds of different enzymes that each break down a single macromolecule, including other proteins, and no matter what type of macromolecule it is, they are broken down largely by the same type of reaction, called hydrolysis.

The dehydration synthesis reaction for two amino acids, in this case glycine on the left, and alanine on the right. (Source)

The proteins we ingest are made up of a combination of 20 different amino acids, each with a unique structure giving its own properties, like whether it is able to be in contact with water or not. They also vary widely in size. Both of these properties are very important in determining the structure and function of the protein by determining how it folds up. Each amino acid is bonded to the next by removing a hydrogen ion (H+ or proton) from one, and a hydroxide ion from another (OH-). The H and OH- spontaneously attract each other to form water, thus giving the reaction the name of dehydration synthesis. The reaction is easily reversed by adding a water molecule back into the bond to cut it (root of hydrolysis = water cutting). Hydrolysis is a thermodynamically favorable reaction, meaning it happens fairly efficiently on its own spontaneously, but enzymes are needed to speed it up to meet our body's demand for new building blocks.

Enzymes in our digestive system that do precisely this include pepsin, trypsin, and chymotripsin, and each specialize in breaking the bond at just a few specific amino acids in the stomach and the duodenum. These enzymes are able to reach virtually all peptide bonds due to the low pH in our stomachs unfolding the protein from its complex shape into more of a chain. The end result is that the protein we ate is broken up into individual amino acids for absorption into the bloodstream through the lining of our intestines. When this happens, they have none of the properties of the protein we ingested, and do not have a function on their own. It doesn't matter which protein it is, or where it came from, it almost always ends up as nonfunctional pieces that are recycled to new dehydration reactions elsewhere in the body to create new proteins. There's an exceptionally small chance for a novel GMO protein to survive the digestive system intact and functional, and GMO proteins are not any more likely than any other protein to do so.

Many food allergies, however, are indeed caused by proteins that do resist full digestion in any one or several of these steps for one reason or another. When this happens, our immune systems recognize that it's a foreign protein and attack it, causing the allergy. It's certainly plausible that this could theoretically happen to any GMO protein, but the risk is not deemed serious enough by the FDA to require a clinical trial for new GMOs. I think it's perfectly reasonable for consumers to demand testing for potential food allergies, but I also think the potential risk is quite a bit overhyped. It's certainly worthy of debate. I'd be open for requiring independently operated small scale clinical trials.

Digesting the nucleic acids DNA and RNA follow a very similar process. They too are polymers where each building block is bound in dehydration reactions, and are broken up by hydrolysis by enzymes called nucleases. The nucleic acids can either be reused to build new nucleic acids, or they can be broken down further into a sugar, the base that makes up the genetic code, and a phosphate group.

Hydrolysis of DNA. An arrow on the bottom left shows a water molecule approaching the phosphate (PO4) group that binds the pair of nucleotides, The pentagon is a sugar, called deoxyribose. The molecular structure of the bases are not shown (Source).

Some critics have claimed that the transgenes have been taken up by bacteria in our digestive system intact, but there is no evidence that they've ever survived through the entire digestive tract. This is a hypothetical and exceedingly unlikely event that currently is not supported by the science. Furthermore, a transgene is no more likely than any other gene we digest to be transferred like this. Also, if, say, the gene providing Roundup resistance in Monsanto's corn were to be transferred in full to a bacteria, how exactly would it provide a survival benefit without constant exposure to Roundup in our digestive systems?

When people claim that the corporations are buying and paying for the science on GMOs, they don't realize it, but they're saying that everything we know over decades of research in molecular biology and digestion is suspect. Because so much of what we do know is fundamental, the FDA long ago declared that GMOs are "substantially equivalent" to any other non-GMO, and required no additional testing. They didn't do it specifically to appease powerful interests, they did it because it would have been irrational for them to do otherwise. Their jurisdiction is public health, and in this case they made the choice with much more science behind it. If you listen to vocal critics of GMOs, it seems they're starting to get this message.

When people say "we have the right to know" what's in our food, hopefully now you can get an idea of why a label saying something is genetically modified doesn't really tell you much except what you already know: this organism was grown using industrial agricultural methods.

4 comments:

Couple thoughts. If genes are being transferred from one organism to another, I don't see why the allergy threats would be different than the existing threats from those two organisms. So, hypothetically, if you're allergic to shellfish, if the DNA to build a protein from a mollusk gets transferred to a salmon it seems you may potentially be allergic to that salmon (but I'd imagine the odds are still very very small) Is there some reason some new protein would be created that didn't already exist in either species that might cause an allergy?

Second. I'm not opposed to genetically modified organisms, in general. The primary threat I see from them isn't through digestion, but instead through altering natural ecosystems. Your salmon example in the prequel to this article could theoretically completely replace the existing population of Atlantic Salmon (if growing faster is naturally selected as preferable). Despite the log odds, it's a bit disconcerting to imagine humans playing an even greater role in displacing natural ecosystems.

I think that just the mere fact that a shellfish gene were present wouldn't be enough to cause the same allergy. I don't really know enough about the particulars of shellfish allergies to say what is and what isn't an allergen about them. I'd be very surprised if it's anything more than a handful of particular proteins or some other molecule.

I totally agree that the primary threat is ecological. I sort of sense a moment, though, as evidenced by Mark Lynas's recent "conversion" that the health argument might possibly be approaching low-hanging fruit territory. I want people on the fence about whether these things are going to harm them if they eat them from time to time to really think about it and be open to a perspective they may not have. I want the debate to occur around genuine risks, with less distraction from dubious ones that may elicit an emotional reaction, but lie outside of decades of understanding of molecular biology, biochemistry, and genetics.